1. Field of the Invention
This invention relates to novel benzoxazine derivatives and pharmaceutically acceptable salts thereof, which are useful as drugs, in particular as potassium channel (K.sup.+ channel) activating agents, and pharmaceutical compositions containing the same as well as to intermediates for the production of these derivatives and salts.
The benzoxazine derivatives and salts thereof according to the present invention are compounds of a novel type which activate K.sup.+ channels and thereby exhibit antispasmodic activity, namely smooth muscle relaxant activity.
2. Background of the Related Art
As smooth muscle relaxants, those acting on the contractile process and those acting on the relaxing process are known. Among drugs in the former category are various excitatory chemical transmitter receptor blockers and calcium antagonists, while inhibitory chemical transmitter receptor stimulants and nitrates are representative of the latter type of drugs.
Recently, a drug which relaxes smooth muscles by activating the K.sup.+ channels has been reported as a new smooth muscle relaxant.
In the thick arteries (particularly the coronary and cerebral arteries) and tracheal smooth muscles in contrast with the general excitable tissues, the K.sup.+ channels function in such a manner that these tissues will not be excited to an unnecessary extent by premature and excessive activation (maintenance of lumen size) but if the physiological function of the K.sup.+ channels is impaired, an electric excitation takes place as intensely as in the general excitable tissues to elicit intense local contractions, viz. spasms. It is acknowledged that spasms of the coronary or cerebral arteries and tracheal smooth muscles induce various diseases such as angina pectoris, cerebrovascular disorder and asthma. It is, therefore, believed that a K.sup.+ channel activating agent should be useful for the prevention and treatment of these diseases.
Among the compounds known to have K.sup.+ channel activating activity, there are 4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol derivatives as disclosed in EP 76075, for instance. The compounds according to the present invention are novel 2H-1,4-benzoxazine derivatives differing in structure from such known compounds.